Drug-gene and drug-drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial

• Published in: Pharmacogenomics Vol. 20; no. 6; pp. 397 - 408
• Main Authors: Fulton, Cathy R, Zang, Yong, Desta, Zeruesenay, Rosenman, Marc B, Holmes, Ann M, Decker, Brian S, Zhang, Yifei, T Callaghan, John, Pratt, Victoria M, Levy, Kenneth D, Gufford, Brandon T, Dexter, Paul R, Skaar, Todd C, Eadon, Michael T
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.04.2019
• Subjects: Adult; adverse side effects; Aged; Aged, 80 and over; Algorithms; Analgesics; Analgesics, Opioid - therapeutic use; Codeine; Codeine - therapeutic use; CYP2D6; CYP2D6 protein; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P450; Drug dosages; Drug Interactions - genetics; Enrollments; Female; Genomics; Genotype & phenotype; Genotyping; Humans; IGNITE; INGENIOUS; Male; Metabolism; Metabolites; Middle Aged; Narcotics; Opioids; Pain; Pharmacogenetics - methods; pharmacogenetics; opioids; Pharmacogenomics; phenoconversion; Prescription drugs; Tramadol; Tramadol - therapeutic use; Working groups; Young Adult; Indiana; pharmacogenomics; IGNITE; CYP2D6; phenoconversion; INGENIOUS; adverse side effects; pharmacogenetics; opioids
• ISSN: 1462-2416; 1744-8042; 1744-8042
• DOI: 10.2217/pgs-2018-0205

Tramadol and codeine are metabolized by CYP2D6 and are subject to drug-gene and drug-drug interactions. This interim analysis examined prescribing behavior and efficacy in 102 individuals prescribed tramadol or codeine while receiving pharmaco-genotyping as part of the INGENIOUS trial (NCT02297126). Within 60 days of receiving tramadol or codeine, clinicians more frequently prescribed an alternative opioid in ultrarapid and poor metabolizers (odds ratio: 19.0; 95% CI: 2.8-160.4) as compared with normal or indeterminate metabolizers (p = 0.01). After adjusting the CYP2D6 activity score for drug-drug interactions, uncontrolled pain was reported more frequently in individuals with reduced CYP2D6 activity (odds ratio: 0.50; 95% CI: 0.25-0.94). Phenoconversion for drug-drug and drug-gene interactions is an important consideration in pharmacogenomic implementation; drug-drug interactions may obscure the potential benefits of genotyping.